Connecting research to society

Elmar Tobi publishes in Nature Communications

27 November 2014 Author: Molepi - Molecular Epidemiology

The department of Molecular Epidemiology proudly announces the publication of Elmar Tobi and Bas Heijmans in Nature Communications.

Please read our press release below:

People born during the Dutch Famine have altered regulation of growth genes

And may have helped these individuals to survive as a fetus. 


Individuals conceived and born in the severe Dutch Famine, also called the Hunger Winter, may have survived this horrendous period of World War 2 by making adaptations to how active their DNA is.  Genes involved in growth and development were differentially regulated. Researchers at the Leiden University Medical Center, Columbia University and Harvard University just published an article in Nature Communications.

During the winter of 1944-1945 the Western part of The Netherlands was struck by a severe 6-month famine. During this Hunger Winter the available rations provided as low as a quarter of the daily energy requirement. Still, children were conceived that were delivered with a normal birth weight. Extensive research on the DNA of these Hunger Winter children shows that the regulatory systems of their growth genes have been altered. This may also explain why they have a higher change on metabolic disease in later life.


Decades later

“The different setting of the growth genes may have helped the Hunger Winter children to withstand the Famine conditions, but these changes may likewise be unfavourable for their metabolism as adults. The altered settings were associated with LDL cholesterol at age 60, for instance”, says principal investigator Dr. Bas Heijmans.


Growth genes seemed different

The research team compared the DNA of the Hunger Winter children, now aged 60, at just over 1 million places, comparing them with same-sex siblings. They were able to see how the genes were differentially regulated in the Hunger Winter children, as compared with their siblings with a similar genetic and familial background.  Groups of genes involved in growth and development showed a different gene activity setting. The Hunger Winter children were all around 60 years of age when they gave blood for DNA research. Their growth genes seem altered for life. “The potential for a gene to become active is mainly determined in the crucial weeks after fertilization. This master regulatory system that determines which genes are on and which are off is called epigenetics and can be compared by a sound technician making adjustments during a recording to get that perfect sound. Environmental factors during development can make a lasting imprint on this system”, says Dr. Bas Heijmans.


Timing matters

Early development is important for later health. A wealth of epidemiological studies points this out. “Thanks to the willingness of the Hunger Winter children and their families to contribute to our studies, we can pin point which phases of development are especially sensitive to the environment. We are currently extending our inquiries not only to those conceived during the famine, but also to those exposed during mid-gestation. A lot of important things are happening in the womb about we know quite little in humans”, says first author Dr. Elmar W. Tobi.


This research was funded by the Netherlands Genome Initiative, the National Institutes of Health and the European consortium IDEAL-ageing.